Relative aggregation state and hemolytic activity of amphotericin B encapsulated by poly(ethylene oxide)-block-poly(N-hexyl-L-aspartamide)-acyl conjugate micelles: effects of acyl chain length.

We systematically altered the chemical structure of the core-forming poly(L-amino acid) block of an amphiphilic diblock copolymer series based on poly(ethylene oxide)-block-poly(N-hexyl-L-aspartamide), PEO-b-p(N-HA), acyl esters by varying the length of the attached acyl side chain. Drug-loaded micelles were prepared in good yield by a modified solvent evaporation procedure. In addition, the relative aggregation state and hemolytic activity of encapsulated amphotericin B (AmB) were analyzed by absorption spectroscopy. The length of the attached acyl side chain in PEO-b-p(N-HA) acyl ester micelles modulates the relative aggregation state of encapsulated AmB. Furthermore, acyl chain length appears to have a profound influence on the time-dependent hemolytic profile of encapsulated AmB toward bovine erythrocytes. For all acyl conjugate micelle-AmB formulations, the onset of hemolysis is delayed relative to free AmB. Particularly in the case of stearate ester micelles, the incomplete and gradual build-up of hemolysis might reflect the sustained release of drug over a period of 24 h. Based on the corresponding absorption spectrum, we speculate that encapsulated AmB may interact strongly with stearate side chains, resulting in sustained release. Via chemical manipulation of the core-forming region, it may be possible to fine-tune the release of encapsulated AmB from PEO-b-p(N-HA)-acyl ester micelles. Copyright 2002 Elsevier Science B.V.